Effects of polyamines on ethylmorphine N-demethylation in rat liver microsomes.
The time course linearity of ethylmorphine N-demethylation was improved by the addition of polyamines to the reaction mixture. The most remarkable effect on the time course linearity of ethylmorphine N-demethylation was observed when spermine was used. The apparent stimulatory effect of spermine was decreased remarkably by the simultaneous addition of EDTA to inhibit lipid peroxidation. Similar results were observed when an additional lipid peroxidation inhibitor such as Co2+, Mn2+ or 2,2'-bipyridine was used in place of EDTA. Hydrogen peroxide-dependent ethylmorphine N-demethylation activity in rat liver microsomes was not influenced by the addition of spermine. In addition, neither lipid peroxides formation nor the stimulatory effects of polyamines on ethylmorphine N-demethylation was observed in the reconstituted monooxygenase system. These results suggest that the inhibitory effects of polyamines on lipid peroxidation might be responsible for the stimulatory effects on drug oxidations.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D005036:Ethylmorphine / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008658:Inactivation, Metabolic; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009022:Morphine Derivatives / Q000378:metabolism*; D051381:Rats; D013096:Spermine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013997:Time Factors
D009022:Morphine Derivatives; D013096:Spermine; D003577:Cytochrome P-450 Enzyme System; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D005036:Ethylmorphine